The drug pantoprazole sodium sesquihydrate (5-(Difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole sodium sesquihydrate) is used in the treatment of gastroesophageal reflux disease (GERD), reflux esophagitis, gastric ulcers, duodenal ulcers and Zollinger-Ellison Syndrome. Pantoprazole is a substituted benzimidazole. Pantoprazole accumulates in the acidic compartment of the parietal cells after absorption and is protonated by specific action on the proton pumps of the parietal cells. Pantoprazole is a proton pump inhibitor, i.e., it inhibits specifically and dose proportionally H+,K+-ATPase, the enzyme which is responsible for gastric acid secretion in the parietal cells of the stomach.
Pantoprazole exerts its full effect in a strongly acidic environment (pH<3) and remains mostly inactive at higher pH values, thereby selectively affecting the acid secreting parietal cells of the stomach. Therefore, the complete pharmacological and therapeutic effect for pantoprazole can only be achieved in the acid-secreting parietal cells. By means of a feedback mechanism this effect is diminished at the same rate as acid secretion is inhibited.
As with other proton pump inhibitors and H2 receptor inhibitors, treatment with pantoprazole causes reduced acidity in the stomach causing a reversible increase in gastrin in proportion to the reduction in acidity. Since pantoprazole binds to the enzyme distal to the cell receptor level, it affects hydrochloric acid secretion independently of stimulation by other substances like acetylcholine, histamine, gastrin. The same effect is observed following oral or intravenous administration. In general, preparation of pantoprazole sodium sesquihydrate and certain of its polymorphic forms is known in the art. However, it is also known that different polymorphic forms of the same drug may have substantial differences in certain pharmaceutically important properties. Therefore, there is a continuing need for new methods of preparation.